Immune modulation mimics damage control orthopaedics’ upregulation of anti-inflammatory miRNA-21/23a/27a and miRNA-30b in the lung after polytrauma in pigs

Introduction: Coagulopathic disorders (CDs) complicate treatment in polytraumatised patients. Against this background, operative strategies for fracture management are controversial in this cohort. This study therefore investigated the effects of two established operative concepts, early total care (ETC) and damage control orthopaedics (DCO), on CD in a large-animal polytrauma (PT) model. Methods: Twenty-two animals (Sus scrofa domesticus) sustained PT involving blunt-chest trauma, liver laceration, bilateral femur fracture, and pressure-controlled haemorrhagic shock. After resuscitation, animals were allocated to ETC (n = 8), DCO (n = 8), or served as a non-traumatised control group (CG, n = 6). Animals were ventilated and monitored under ICU standards for 72 h. Blood samples were collected at baseline and post-trauma after 1.5, 2.5, 24, 48, and 72 h. Plasminogen activator inhibitor-1 (PAI-1) and thrombin-antithrombin (TAT) complex concentrations were determined by ELISA. Results: Compared to the CG, ETC and DCO subjects had significantly increased plasma concentrations of PAI-1 after 2.5 h (CG vs. ETC: p = 0.0050, CG vs. DCO: p = 0.0016). Furthermore, the ETC group showed significantly increased plasma PAI-1 concentrations after 24 h compared to the CG and DCO groups (CG vs. ETC: p = 0.0002, DCO vs. ETC: p = 0.0004). During the later clinical course, concentrations of TAT were significantly increased in the ETC group compared to the CG and DCO group after 72 h (CG vs. ETC: p = 0.0290, DCO vs. ETC: p = 0.0322). Conclusion: PT is strongly associated with CD in the early post-traumatic course. In comparison to DCO, ETC appeared to be negatively associated with CD. Future studies must investigate this impact, especially in those patients admitted with trauma-induced coagulopathy, to improve outcomes.

Hyperoxia induces lung injury through lung inflammation in premature infants, leading to bronchopulmonary dysplasia (BPD). Semaphorin 3A (SEMA3A) participates in diverse biological processes, including cell migration, angiogenesis, and inflammation. The effect of SEMA3A on hyperoxic lung injury of neonatal rats with BPD was investigated in this study. Neonatal rats with BPD were established through hyperoxia treatment. Hematoxylin-eosin staining was used to evaluate histopathological analysis in lung tissues. SEMA3A expression was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Adeno-associated virus (AAV)-mediated over-expression of SEMA3A (AAV-SEMA3A) was administrated into hyperoxia-induced rats, and apoptosis was evaluated by TUNEL staining. Levels of inflammatory cytokines were investigated by enzyme-linked-immunosorbent serologic assay (ELISA). Hyperoxia-induced histopathological changes in lung tissue reduced alveolar number and enhanced alveolar interval and alveolar volume. SEMA3A was downregulated in lung tissue of hyperoxia-induced rats. AAV-SEMA3A injection attenuated hyperoxia-induced cell apoptosis in lung tissues by increasing Bcl-2 and decreasing Bax and cleaved caspase-3. Moreover, the enhanced levels of Interleukin (IL)-1β, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor-α (TNF-α) in hyperoxia-induced rats were restored by AAV-SEMA3A injection by the downregulation of nuclear factor kappa B (NF-κB) phosphorylation. AAV-SEMA3A injection also ameliorated histopathological changes in lung tissues of hyperoxia-induced rats by increasing the number of radial alveolar count and decreasing the volume of mean linear intercept. Besides, the protein expression levels of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) phosphorylation were reduced in hyperoxia-induced rats post-AAV-SEMA3A injection. Ectopical expression of SEMA3A suppressed hyperoxia-induced apoptosis and inflammation in neonatal rats, and ameliorated the histopathological changes through inactivation of ERK/JNK pathway.

<h3>Objectives</h3> The animal model of silicosis of non-exposed tracheal instillation induced by SiO₂ in rats lung fibrosis were studied. To investigate: whether SiO₂ can induce fibrosis in lung tissue by induction of epithelial interstitial transformation (EMT); EMT in poly guanine nucleotide (PolyG) molecular biology mechanism of silicosis fibrosis reversal. the effects of PolyG preventive and therapeutic interventions on EMT in rats exposed to silica dust and the effect of intervention at different time points. <h3>Methods</h3> Ninety-six healthy male Sprague-Dawley (SD) rats weighing 180~220 g were randomly divided into normal saline group (n=32), silicosis model group (n=32), PolyG prevention group (n=16) and PolyG (28 days) treatment group (n=16). After the rats were anaesthetised with ether, the control group was injected with 1 ml normal saline by bronchial instillation. The rats in other groups were treated with non-exposed tracheal infusion of a one-time infusion of 50 ml/L silica suspension 1 ml. The rats in the PolyG preventive group were treated with PolyG 2.5 mg/kg body weight (the weight of each rat was determined 28 days after modelling) at the same time by tail vein injection. The rats in the PolyG treatment group were treated with intravenous injection of PolyG 2.5 mg/Kg body weight (by modelling 28 days after each rat weight to determine the appropriate dose). The rats in the polyG prevention group and the treatment group were sacrificed on the 28th day and the 56th day after the corresponding administration. Silicosis model group and saline control group also have 8 rats were sacrificed at the same time point.(Macrophage receptor with collagenous structure, MARCO), E-cadherin (E-cadherin) were detected by Western blotting. The macrophage receptor (MARCO) Cadherin, E-cadherin, α-smooth muscle actin (α-SMA), vimentin and type I and type III collagen; the right amount of lung tissue, The relative expression levels of E-cadherin, α-SMA, vimentin and type I and type III procollagen mRNA were detected by Real-time PCR. The right middle lobe tissue was fixed with 4% paraformaldehyde, paraffin section, the histopathological changes of lung tissue were observed by HE staining and Masson staining. Immunohistochemical staining was used to detect the localization and expression of E-cadherin, α-SMA and vimentin in lung tissue. <h3>Results</h3> Histopathological changes of lung tissue in different groups: The lung tissue structure of the rats in the control group was normal, and the infiltration of inflammatory cells was observed in the surrounding area, and the lung tissue structure of the control group did not change significantly over time; There were a large number of inflammatory cell infiltration in the lung tissue of the rats in the silicosis model, and the typical fibrous nodules were formed. The nodules were composed of macrophages and fibroblasts. Some areas of the alveolar structure still existed, showing different alveolar walls and small blood vessel wall thickening; with the dying time, the number of fibrous silicon nodules increased, some of the silicon nodules have a trend of integration and becoming bigger, in particular, is completely fibrous tissue, or even fibrotic changes; In PolyG prevention group and treatment group, the number of cell nodules or silicon nodules was lower than that of the model group; the degree of lesion in the rats was significantly lower than that in the control group. The results of immunohistochemistry showed that α-SMA and vimentin positive cells were significantly increased in the silicosis model group, and the number of E-cadherin positive cells was significantly decreased. After administration of PolyG, the number of E-cadherin-positive cells and the number of α-SMA and vimentin-positive cells were significantly increased. The expression of MARCO, E-cadherin, α-SMA and vimentin in the lung tissue of the control group were not significantly different (p&lt;0.05). There was no significant difference in the expression of MARCO and EMT-related proteins in rat lung tissue at different time points (p&lt;0.05). The levels of E-cadherin in the lung tissue of the silicosis model group were increased with the prolongation of observation time (p&lt;0.05). The expression levels of MARCO, α-SMA and vimentin protein in the lung tissue of the PolyG intervention group (prophylactic and therapeutic) were lower than those in the control group, but the E-cadherin was higher than that of the silicosis group model group (p&lt;0.05). The comparison of mRNA expression levels of E-cadherin, α-SMA and vimentin in lung tissue of different groups: the expression of E-cadherin, α-SMA and vimentin mRNA in lung tissue of all groups were the same as those of corresponding protein. The expression of collagen I and III in the lung tissue of different groups were significantly higher than those in the control group (p&lt;0.05). There was no significant difference in the expression of collagen I and III in rat lung tissue of control groups at different time points (p&lt;0.05). The expression level of collagen I and III in the lung tissue of silicosis model group increased with the prolongation of dying time (p&lt;0.05). The protein content of collagen I and III in PolyG intervention group was significantly higher than that in the control group (p&lt;0.05). The mRNA expression of type I and III procollagen were the same as that of I and III collagen. <h3>Conclusions</h3> The protein content and mRNA expression of E–cadherin were decreased, while α–SMA and vimentin in silicosis model group were increased, which indicated that there was epithelial–mesenchymal transition in the development of silicosis. After inhibition of MARCO combined with SiO₂, the protein content and mRNA expression of α–SMA and vimentin were significantly down–regulated, and the protein content and mRNA expression of E–cadherin were significantly up–regulated; I, III collagen content and I, III type procollagen mRNA expression levels were decreased and lung tissue pathological changes were reduced in vary degrees. PolyG intervention (prophylactic and therapeutic) can effectively inhibit the progression of EMT, and further delay the formation of pulmonary fibrosis, and the effect of early to give preventive intervention is better.

The objective of this study was to investigate the effects of prolonged exposure to the oxidative agent NaClO on histopathological changes in the lung tissues of laboratory animals. Specifically, the study aimed to examine morphological changes in the pulmonary microcirculation and the level of vascular cell adhesion molecule-1 (VCAM-1) as a functional activity indicator of endothelial cells in animals with induced systemic sclerosis (SSc). A laboratory animal model was used to assess the impact of long-term exposure to NaClO on lung tissues. The animals were divided into three groups: the experimental group (25 rats) was exposed to NaClO, while the control group (20 rats) received an isotonic solution, and the intact group (15 animals) was without any exposure. The concentration of VCAM-1 in the serum of the animals was measured using an enzyme-linked immunosorbent assay. Histopathological analysis of lung tissue specimens was performed using both light and electron microscopy. The concentration of VCAM-1 in the serum of the animals in the experimental group was significantly higher than that of the control group (91.25 [85.63-143.75] vs 19.50 [13.53-22.20], p < 0.05). The histopathological analysis revealed significant abnormalities in the lung tissue specimens from the experimental group, including disruption in the structure of the hemocapillaries of the lungs, narrowing of the microvessel lumen, and perivascular infiltration by polymorphonuclear cells. The electron microscopic analysis showed several ultrastructural changes in the endotheliocytes of the hemocapillaries, including uneven expansion of the perinuclear space, swollen mitochondria, and fragmentation of the membranes of the granular endoplasmic reticulum. Additionally, the basement membrane of hemocapillaries showed uneven thickening with indistinct contours, and the peripheral parts of endotheliocytes were marked by numerous micropinocytotic vesicles and vacuoles. Erythrocyte aggregates and leukocyte adhesion were identified in the lumen of many hemocapillaries, while adhesion and aggregation of platelets were also observed in several hemocapillaries. Long-term exposure to NaClO can cause significant histopathological changes in lung tissues, including damage to the hemocapillaries and disruption in the structure of endotheliocytes.

Objective: To investigate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in the lung tissue of rats with acute diquat (DQ) poisoning and the distribution of diquat in lungs. Methods: Fifty-four fasted male Wistar rats were randomized into control group (n=6) and exposure group (n=48) . According to the time point, the exposure group was divided into 2 h, 4 h, 12 h, 1 d, 3 d, 7 d, 11 d and 14 d groups with 6 rats in each group. Exposure groups were administered 11.55 mg/kg DQ (1 ml/100 g BW) by single-dose of intragastric administration, while the control group rats were given normal saline. The histopathological changes of lung tissue of rats in each group were observed. The expression of nrf2 in lung tissue was detected by immunohistochemistry, and the diquat concentration in lungs was determined by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS) . Results: In the exposure group, DQ was detected in lungs on 2 hours after poisoning. The concentration of DQ in lung tissue decreased gradually over time, and there was no accumulation in lung tissue. The histopathological changes of lung tissue were not obvious in the early stage of poisoning. The injury was the most serious on the 3rd day, a large number of inflammatory cells could be seen in alveolar cavity and lung stroma, and the pathological injury of lung tissue began to be alleviated on the 7th day. The results of immunohistochemistry showed that Nrf2 was mainly expressed in the nucleus of pulmonery cells. The expression of Nrf2 in the exposure group was significantly higher than the control group. The expression of Nrf2 increased significantly at the 12th hour (P<0.05) , reached the peak on the 3rd day (P<0.05) . There was no difference between the control group and the 14th day (P>0.05) . Conclusion: There was no accumulation of DQ in the lung tissue for a long time, and there was a hysteresis in lung injury induced by redox reaction of DQ. Nrf2 was highly expressed in the lung tissue of rats with acute DQ poisoning, which was correlated with histopathology injury of lung tissue, suggesting that Nrf2 plays an important role in antagonizing acute lung injury induced by DQ.

Objectives: To find the correlation of manner of death with histopathological changes in fatal burns in atertiary care hospital in north India.Method: This was a comparative study. Cases were thoroughly studied usingspecially designed proformathat included the demographic profile of deceased along with information gathered from relatives, police& hospital records and autopsy findings. Before taking the lung sample, proper consent was taken fromthe relatives after explaining the purpose of the study. After gross examination, sections were taken fromdifferent lobes of lungs.Results: Tracheal congestion was found mainly in accidental deaths (49.77%), followed by suicidal deathswith 28.57% and homicidal deaths with 21.66%. This difference was found to be statistically significant(p<0.001). Lung Consolidation was more commonly seen in accidental and suicidal deaths (48.4%) ascompared to homicidal deaths (3.19%). Various other variables were also correlated with type of burns.Conclusion: This association of histopathological changes in lung tissue could help to ascertain the modeof Death, as well as can hint towards conduction of proper inquest in suspicious cases of so called suicidaldeaths

Bilateral femoral shaft fracture in polytrauma patients: Can intramedullary nailing be done on an emergency basis?

This study aimed to isolate and diagnose the bacterial pathogens that causes pneumonia in sheep, study the biochemical and histopathological changes in lung tissue of infected animals and determining the most effective types of antibiotics for treating sheep diseased with pneumonia. 150 samples (50 nasal swabs, 50 tracheal samples, 50 lungs samples from slaughtered sheep) were collected randomly from different areas of Salah Aldeen governorate during the period (September 2019 till January 2020) . The results showed that no significant differences in the values between positive and negative results from nasal, tracheal and infected lungs at a probability level P&lt; 0.05. And showed that Staphylococcus aureus and Klebsiella pneumonia are two main bacterial causes of pneumonia in sheep . In macroscopic examination the prominent lesion in most lung samples was congestion and presence of emphysema with an expansion of the bronchitis and found that the most common type of pneumonia infection is broncho pneumonia. All the isolated bacterial species; however, show sensitivity to the antibiotics chloramphenicol and trimethoprim + sulfamethoxazole except Pasteurella Spp., that it shows resistance to trimethoprim+ sulfamethoxazole.

BackgroundRespiratory failure can be a severe complication after polytrauma. Extensive systemic inflammation due to surgical interventions, as well as exacerbated post-traumatic immune responses influence the occurrence and progression of respiratory failure. This study investigated the effect of different surgical treatment modalities as well as combined inhibition of the complement component C5 and the toll-like receptor molecule CD14 (C5/CD14 inhibition) on the pulmonary microRNA (miRNA) signature after polytrauma, using a translational porcine polytrauma model.MethodsAfter induction of general anesthesia, animals were subjected to polytrauma, consisting of blunt chest trauma, bilateral femur fractures, hemorrhagic shock, and liver laceration. One sham group (n=6) and three treatment groups were defined; Early Total Care (ETC, n=8), Damage Control Orthopedics (DCO, n=8), and ETC + C5/CD14 inhibition (n=4). Animals were medically and operatively stabilized, and treated in an ICU setting for 72 h. Lung tissue was sampled, miRNAs were isolated, transcribed, and pooled for qPCR array analyses, followed by validation in the individual animal population. Lastly, mRNA target prediction was performed followed by functional enrichment analyses.ResultsThe miRNA arrays identified six significantly deregulated miRNAs in lung tissue. In the DCO group, miR-129, miR-192, miR-194, miR-382, and miR-503 were significantly upregulated compared to the ETC group. The miRNA expression profiles in the ETC + C5/CD14 inhibition group approximated those of the DCO group. Bioinformatic analysis revealed mRNA targets and signaling pathways related to alveolar edema, pulmonary fibrosis, inflammation response, and leukocytes recruitment. Collectively, the DCO group, as well as the ETC + C5/CD14 inhibition group, revealed more anti-inflammatory and regenerative miRNA expression profiles.ConclusionThis study showed that reduced surgical invasiveness and combining ETC with C5/CD14 inhibition can contribute to the reduction of pulmonary complications.

Objective To observe the expression of heat shock protein 70 (HSP70) in lung of rats after paraquat (PQ) poisoning and to investigate the therapeutic effects of ulinastatin. Method Seventy-two adult healthy SD rats were randomly(random number) divided into control group (group A, n = 24), poisoning group (group B, n =24) and ulinastatin group (group C, n =24). The rat models of acute PQ poisoning were established by intra-gastric administration of 80 mg/kg PQ to rats of group B and group C, and the rats of group C were intra-peritoneally injected with 100 000 IU/kg ulinastatin 30 minutes after poisoning. The expression of HSP70 in lung tissue was observed, and W/D and histopathological changes in lung tissue were compared 12 h,24 h,48 h and 72 hours after poisoning. The expression of HSP70 in lung tissue was assayed by using RT-PCR. All quantitative data were processed with one-way analysis of variance to compare multiple sample means. Results Compared with group A, the expression of HSP70 in the lung of rats in group B and group C increased significantly at all intervals ( P ＜ 0.05). The pathological changes in lung tissue of rats with PQ poisoning showed mainly congestion,leukocytes infiltration and local hemorrhage, and the pathological changes in lung tissue of group C were significantly lessened. Conclusions Ulinastatin may ameliorate the acute lung injury to a certain extent after PQ poisoning in rats by enhancing the expression of HSP70. Key words: Paraquat; Poisoning ; Ulilnastatin; Heat shock protein; Acute lung injury

To investigate the roles and underlying mechanisms of mixed lineage kinase domain like (MLKL)-mediated inflammatory response induced by NOD-like receptor protein 3 (NLRP3) inflammatory corpuscles in the acute lung injury (ALI) after sepsis. Eighteen BALB/c mice were randomly divided into sham operation group (Sham group), cecal ligation and perforation (CLP)-induced sepsis model group (CLP group) and specific inhibitor Necrostatin-1 intervention group [CLP+Nec-1 group, Necrostatin-1 solution (20 mg/kg) was injected intravenously 10 minutes before modeling], with 6 mice in each group. The mice were sacrificed by neck amputation at the 2nd day after operation, and the serum and lung tissue samples were collected. The morphological changes of lung tissue were observed by hematoxylin-eosin (HE) staining. The water content of lung tissue was detected by dry-wet weight method. The pulmonary vascular permeability was measured by Evans blue (EB) staining. The protein expressions of MLKL and NLRP3 in the lung tissue were detected by Western blotting, and the level of serum interleukin-1β (IL-1β) was detected by enzyme linked immunosorbent assay (ELISA). HE staining showed that the lung morphological structure in Sham group was normal. In CLP group, congestion and edema in the alveolar cavity and interstitium, infiltration of neutrophils and thickening of alveolar wall were observed. The histopathological changes of lung tissue in CLP+Nec-1 group were better than those in CLP group. Compared with Sham group, the water content of lung tissue [(88.00±0.00)% vs. (78.00±0.01)%], pulmonary vascular permeability [EB content (mg/L): 11.82±1.15 vs. 4.00±0.71], the protein expressions of phosphorylated MLKL (p-MLKL) and NLRP3 in lung tissue (p-MLKL/GAPDH: 0.34±0.04 vs. 0.12±0.01,NLRP3/GAPDH: 0.47±0.07 vs. 0.16±0.04), and the level of serum IL-1β (ng/L: 183.56±9.61 vs. 44.14±6.95) in CLP group were all significantly increased (all P < 0.01). Compared with CLP group, the water content of lung tissue [(81.00±0.01)% vs. (88.00±0.00)%], pulmonary vascular permeability [EB content (mg/L): 7.90±0.00 vs. 11.82±1.15], protein expressions of p-MLKL and NLRP3 in lung tissue (p-MLKL/GAPDH: 0.13±0.03 vs. 0.34±0.04, NLRP3/GAPDH: 0.18±0.04 vs. 0.47±0.07), and the level of serum IL-1β (ng/L: 113.81±6.62 vs. 183.56±9.61) were all significantly decreased (all P < 0.01). MLKL-NLRP3-mediated necroinflammation was significantly up-regulatedin the lung tissue of septic mice, which could be attenuated by specific inhibitor Necrostatin-1.

In this study we examined the ability of selenium and vitamin E to prevent sepsis-induced changes in lung tissue. Fifty rats were divided into five groups: Group 1: Control group; Group 2: Sepsis group. In this group only cecal ligation and perforation (CLP) was performed. Group 3: Selenium group. An intraperitoneal dose of 100 µg selenium was given for the first two days followed by a daily dose of 40 µg for the next five days. CLP was performed the following day. Group 4: Selenium and vitamin E group. In addition to selenium, vitamin E was given intramuscularly in a dose of 250 mg/kg/day for seven days. CLP was performed the following day. Group 5: Vitamin E group. Vitamin E was given intramuscularly in a dose of 250 mg/kg/day for seven days. CLP was performed the following day. There were significant differences between Group 2 and all other groups in terms of blood gas values (pH, pCO2, SaO2), and leukocyte, C-reactive protein (CRP) and glutathione peroxidase levels (p < 0.005). There was no statistically significant difference between groups 3, 4 and 5 in terms of histopathological changes in lung tissue (p > 0.05), but all groups were significantly different compared with Group 2 (p < 0.05). Sepsis-induced lung tissue damage can be reduced or prevented by pre-treatment with of selenium and/or vitamin E in a rat model.

To investigate the role of IL-9 in chronic obstructive pulmonary disease (COPD), and to explore its potential mechanism. A mouse COPD model was established by exposure to cigarette smoke. COPD mice were then randomly assigned into two groups, including: the PBS group and the IL-9 antibody group. The above two groups were treated with phosphate-buffered saline (PBS) or IL-9 injection, respectively. The histopathological changes in lung tissues of mice were observed by hematoxylin-eosin (H&E) staining. Immunohistochemistry was performed to detect IL-9-positive (IL-9+) cells in lung tissues. Expression levels of IL-9, sIL-9R, STAT3, and p-STAT3 in peripheral blood of mice were determined by quantitative Real time-polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blot, respectively. In addition, the expression levels of superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS) were detected. H&E staining results showed that the airway wall structure of COPD mice in the PBS group was irregular. Ciliated columnar epithelium exhibited marked degeneration, necrosis and shedding. Besides, numerous inflammatory cell infiltration, narrowing and rupture of the alveolar septa, and larger cysts fused by adjacent alveoli were observed. H&E staining also indicated that the structure of alveolar epithelium was severely impaired in COPD mice. However, the pathological changes in lung tissues of mice in the IL-9 antibody group were much milder than those of the PBS group. Immunohistochemistry results showed a significant deposition of IL-9+ cells in the lung tissues of the PBS group. Meanwhile, the mRNA and protein levels of IL-9, sIL-9R, and p-STAT3 in the PBS group were also remarkably higher than those of the IL-9 antibody group. In addition, SOD content in the PBS group was significantly decreased, whereas the levels of MDA and ROS were significantly increased than those of the IL-9 antibody group. IL-9 activated STAT3 and aggravated lung injury in COPD mice by increasing inflammatory and oxidative stress.

The optimal treatment of major fractures in patients with blunt multiple injuries continues to be discussed. The aim of this study is to investigate the clinical course of polytrauma patients treated at a Level I trauma center within the last two decades regarding the effect of changes in the management of their femoral shaft fracture. In a retrospective cohort study performed at a Level I trauma center, the patient's injuries and clinical outcomes were studied. Adult blunt polytrauma patients were included if a femoral shaft fracture eligible for intramedullary stabilization was stabilized (including external fixation) primarily < 8 hours after primary admission. Patients were separated according to the management strategies for the femur fracture (I degrees intramedullary nailing [I degrees IMN]; I degrees external fixation [I degrees EF]; I degrees plate osteosynthesis [I degrees plate]) followed during a certain time period: (1) early total care (ETC) (January 1, 1981-December 31, 1989) and early (< 24 hours) definitive stabilization; (2) intermediate (INT) (January 1, 1990-December 31, 1992) change in the protocol; or (3) damage control orthopedic surgery (DCO) (January 1, 1993-December 31, 2000), early (< 24 hours) temporary stabilization, and secondary conversion to intramedullary nailing in patients at risk of organ failure. The patient groups were comparable regarding age, gender distribution, and the mechanism of injury. Primary external fixation was performed significantly more frequent in the INT (23.9%) and DCO (35.6%) groups compared with the ETC group (16.6%) ( = 0.02 ETC vs. DCO). Plating of the femur was almost abolished in the 1990s (DCO, 6.8%; ETC, 23.4%). In the subgroups categorized to I degrees EF (ETC, 41.1 points; INT, 37.1 points; DCO, 39.1 points), the general injury severity was higher in comparison with the I degrees IMN group (ETC, 38.3%; INT, 36.1%; DCO, 35.8%). Thoracic or abdominal injuries accounted for significantly higher numbers of patients submitted to I degrees EF in the INT (13.6%, = 0.03) and DCO (17.3%, = 0.01) groups, compared with the ETC (8.1%) group. A higher incidence of reamed nailing was present in the ETC group compared with the other groups (ETC, 96.1%; INT, 73.7%; DCO, 13.5%). No significant differences in the incidence of local complications were found. The incidence of multiple organ failure decreased significantly from the ETC to the DCO period regardless of the type of treatment of the femoral fracture. Moreover, there was a significantly higher incidence of acute respiratory distress syndrome (ARDS) when I degrees IMN (15.1%) and I degrees EF (9.1%) in the DCO subgroup were compared. A significant reduction in the incidence of general systemic complications regardless of the type of femur fixation used was found when comparing the time periods of 1981 to 1989 (ETC), 1990 to 1992 (INT), and 1993 to 2000 (DCO). The change in treatment protocols to external fixation and from reamed to unreamed nailing was not associated with an increased rate of local complications (pin-track infections, delayed unions, nonunions). Among other causes for the improved general outcome during the most recent time period (DCO), an increase in the frequency of air rescue, a change from reamed to unreamed nailing, and an increased awareness toward thoracic and abdominal injuries may have played a role. Even during the DCO era, IMN was associated with a higher rate of ARDS than I degrees EF. In view of a lower complication rate despite higher injury severity compared with the ETC period, the introduction of DCO appears to be an adequate alternative for patients at high risk of developing posttraumatic systemic complications such as ARDS and multiple organ failure.

Baicalin alleviated APEC-induced acute lung injury in chicken by inhibiting NF-κB pathway activation